Reading disability (RD), also known as dyslexia, is the most common learning disability affecting school children. In the US, Canada, Europe and countries where it has been studied, the incidence is between 5% and 17%. The most prominent feature is difficulty learning to read despite adequate opportunity, instruction, and intelligence. Yet frequently RD goes unrecognized - even by good teachers - leading to poor school performance and in many cases, low self-esteem. Intervention programs have been shown to work, but are most effective when RD is recognized and treated at an early age. Recently, we identified a gene, called DCDC2, and allelic variations that are strongly associated with RD. We developed methods for accurately determining who is a carrier of RD alleles and that could be used for early diagnosis. At least two other RD genes have been identified as well: KIAA0319 and DYX1C1. RD alleles from all three genes are frequently present in RD subjects in the US and Canada, and the UK. Overall, genetic factors account for 44% to 75% of RD. We hypothesize that children at risk for RD could be identified early - when intervention is most useful - by genetic screening for RD alleles from these three genes; and, that an accurate cost-effective genetic screening tool would have wide commercial applications. In Phase I of this SBIR project we propose to 1) assemble and optimize a panel of genetic markers comprised of RD alleles from DCDC2, KIAA0319, and DYX1C1. We will then 2) apply the marker panel to an extant RD DNA collection to identify molecular profiles that would be predictive of RD risk, and to confirm in an independent extant collection. Both of these collections are from subjects that have been thoroughly characterized for RD at internationally recognized reading centers in the US. We anticipate that this Phase I application will lead to the development of an RD molecular profile tool that is suitable for population screening, enabling early diagnosis and effective interventions. Reading disability (RD), also known as dyslexia, is the most common learning disability affecting school children. In the US, Canada, Europe and countries where it has been studied, the incidence is between 5% and 17%. Yet frequently RD goes unrecognized leading to poor school performance. Intervention programs work, but are most effective when RD is recognized and treated at an early age. Most of RD is genetic in origin. We propose to enable early diagnosis and treatment by developing a low-cost genetic screening tool for detecting RD with wide commercial application. [unreadable] [unreadable] [unreadable]